Sir,
The aim of this study is to report the 6-month anatomic and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) response after the combination of intravitreal adalimumab and bevacizumab (IVBA) in patients with macular edema of various etiologies.
Case report
We reviewed the clinical records of consecutive patients with macular edema of various etiologies, which were treated with at least one off-label combined intravitreal injection of 1.25 mg/0.05 ml of bevacizumab and 2 mg/0.08 ml of adalimumab (Figure 1). Five consecutive patients (7 eyes), and at least 6 months of follow-up were identified and included for this analysis.
Our results are depicted in Table 1. Eyes 1 and 7 were previously treated with intravitreal bevacizumab (3 doses with 6-week intervals), with no anatomical or functional response ≥12 weeks from last injection. Four (57.1%) of seven eyes gained ≥3 ETDRS lines of BCVA. None of the patients developed systemic complications such as thromboembolic events or a cerebral vascular accident, and none developed any ocular complication.
Comment
Sfikakis et al1 reported an improvement in visual acuity and macular edema in four patients with refractory DME, following two intravenous infusions of infliximab (5 mg/kg) given 1 month apart. Wu et al2 did not find any visual benefit with either 1 or 2 mg of infliximab or 2 mg of adalimumab in eyes with refractory DME. In addition, a high rate of intraocular inflammation was seen in eyes injected with infliximab.
Androudi et al3 reported five patients with refractory cystoid macular edema secondary to noninfectious uveitis that were treated with intravitreal adalimumab for 3 months with no apparent benefit. There were no important adverse events reported in this small group of patients.
No important adverse events, including inflammation, were reported in our current series.
The limitations of our study include its small sample size, and retrospective nature. In addition, although our study suggests there is a benefit from combined VEGF and TNF-α inhibition, it is unclear if the same benefit could have been obtained with either agent or only with both. Furthermore, several of the etiologies have a documented natural history to suggest that spontaneous resolution is possible. However, two eyes did not respond to prior treatment with bevacizumab alone and did respond to combined VEGF and TNF-α inhibition. Our results warrant further study.
References
Sfikakis PP, Markomichelakis N, Theodossiadis GP, Grigoropoulos V, Katsilambros N, Theodossiadis PG . Regression of sight-threatening macular edema in type 2 diabetes following treatment with the anti-tumor necrosis factor monoclonal antibody infliximab. Diabetes Care 2005; 28: 445–447.
Wu L, Hernandez-Bogantes E, Roca JA, Arevalo JF, Barraza K, Lasave AF . Intravitreal tumor necrosis factor inhibitors in the treatment of refractory diabetic macular edema: a pilot study from the Pan-American Collaborative Retina Study Group. Retina 2011; 31: 298–303.
Androudi S, Tsironi E, Kalogeropoulos C, Theodoridou A, Brazitikos P . Intravitreal adalimumab for refractory uveitis-related macular edema. Ophthalmology 2010; 117: 1612–1616.
Acknowledgements
This study was supported in part by the Arevalo-Coutinho Foundation for Research in Ophthalmology, Caracas, Venezuela.
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The authors declare no conflict of interest.
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Presented in part at the 44th Retina Society Annual Scientific Meeting, Rome, Italy, September 2011.
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Arevalo, J., Serrano, M. & Wu, L. Combined inhibition of tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF) for the treatment of macular edema of various etiologies: a short-term pilot study. Eye 27, 569–571 (2013). https://doi.org/10.1038/eye.2012.301
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DOI: https://doi.org/10.1038/eye.2012.301
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